1. Field of the Invention
The present invention relates to a lung simulator and, more specifically, to a system for simulating lung performance more realistically by accounting for a hypothetical patient's response to a physiological CO2 partial pressure.
2. Description of Related Art
In recent years, the demographic trend of industrial countries has led to an explosion of health-care costs. A comparison between the trend of health-care costs and the aging of the population shows that a large percentage of this cost increase results from hospital stays by elderly people. The length of these stays can be reduced by optimum care administered in the hospital and by suitable follow-up care of the patient at home. Modern medical technology can make an essential contribution to this care.
One sub-sector of health-care technology is respiratory care. Both in intensive medicine and in the home-care sector, respiratory equipment is utilizing an increasing number of bio-parameters, such as the oxygen or carbon dioxide content in the respiratory air. These parameters can be used, for example, to automate the respiration process. For example, the EtCO2 (end-tidal Carbon Dioxide) value is used in new weaning methods which are designed to wean the patient off the respirator unit as quickly as possible. But in the home-care sector, too, innovations are always being developed to meet the ever-increasing requirements for medical equipment. Equipment innovations must be tested for function, safety and handling. It is also possible to provide better training for future users of the medical equipment with suitable simulators. One of these innovations is the implementation of respiratory regulation in lung simulators based on the EtCO2 value.
As background information relating to the simulation aspects relating to the present invention, the physiological principles of respiration are provided herein. Human respiration reacts differently as a function of external factors. Changes in the ambient conditions, such as the air and the partial pressure, also lead to a change in respiration. The atmospheric ambient air which is required for the maintenance of life has the composition described in the following table.
Percentage by volume [%] Type of gas20.96Oxygen [O2]78.00Nitrogen [N2]0.04Carbon dioxide [CO2]1.00Noble gasesA change in the gas mixture such as, for example, an increase of the CO2 content by 5%, would result in severe respiratory distress. Instead of the percentage by volume, the composition of air is also frequently discussed in terms of pressures or of the partial pressure.
In medical applications, the composition of a gas mixture is described in terms of partial pressures. Air is a mixture of gases, and each individual gas exerts a proportion of the total pressure that corresponds to its percentage by volume. The partial pressure accounted for by the individual gas is the partial pressure. The SI Unit of pressure is Pascal (Pa), although in medicine, the older unit mmHg (millimeters of a column of mercury) is commonly used. The partial pressure is calculated according to Dalton's Law:Ptotal=PO2+PN2+PCO2+PNoble gases  (1)However, consideration must be given to the fact that the total pressure is influenced by the moisture that is contained in the air, i.e., the water vapor.
The term “water vapor” refers to the water that is in the gas phase. The partial pressure that is produced by the water vapor is a function of the temperature. In respiratory physiology, it is conventional to indicate the partial pressures of the expiration gas (i.e., gas that is exhaled) without any consideration of the water vapor partial pressure. FIG. 1 shows the water vapor partial pressure as a function of the temperature.
In medicine, the temperature is taken into consideration as an essential factor in three measurement conditions. The volume of a given amount of gas is a function of the temperature as well as of the pressure. Therefore, the ambient conditions must always be indicated in measurements or for theoretical considerations. There are three conventional measurement conditions in respiratory physiology. STPD (Standard Temperature, Pressure Dry) conditions are the physical standard conditions at which the volume data are referenced to T=273 K, P=760 mmHg and PH20=0 mmHg (dryness). Under BTPS (Body Temperature, Pressure Dry) conditions, in the lung, T=310 K and “P” is a variable that is linked to the current barometric pressure and PH20=47 mmHg (water vapor saturation at 37° C.). ATPS (Ambient Temperature, Pressure Saturated) conditions take into consideration the current measurement conditions outside the body, i.e., the volume is measured at ambient temperature, current barometric pressure and water vapor saturation. The aforementioned external ambient conditions (i.e., air and partial pressure) have a major influence on the processes in the body. Respiratory function and the respiratory system must adapt to these conditions.
The basic principles of respiratory function and the mechanical action of the respiratory system that takes place during respiration will now be discussed. Defined in very general terms, respiration is the exchange of gas between the cells in the body and the environment. During inspiration, the lung expands so that fresh air reaches the gas exchange areas, the space in which O2 and CO2 are exchanged. The rising of the costal arch during costal respiration or the falling of the diaphragm during abdominal respiration leads to an expansion of volume in the chest cavity. The space created by the volume expansion is used by the lung parts for expansion. The expansion leads to a pressure reduction in the lung and thus to a ventilation of the lung with fresh air. Correspondingly, the lowering of the costal arch or the lifting of the diaphragm leads to a reduction of the volume of the chest cavity and thus to exhalation.
The air travels via the trachea into the two main bronchi and is then distributed to the increasingly smaller branches of the bronchial tract. Structured like a tree, where the trunk represents the trachea, the bronchial tree branches out in a similar fashion. The alveoli begin with the 20th branching. This space is used primarily for the exchange of gas and is designated the respiration zone. From this point, the diffusion becomes increasingly important, while previously the dominant factor was convection. The spaces, such as the trachea, that do not participate in the gas exchange are designated anatomical dead space.
The anatomical dead space is the space in which no gas exchange takes place, and is important for an understanding of the individual respiratory gas fractions, in particular of the carbon dioxide fraction. The dead space includes the trachea, the mouth, the nose or the bronchi, the total volume of which is approximately 150 ml in an adult. Assuming that fresh gas is in the dead space, which is expired into the gas that is present in the alveoli, the volume of a specified amount of gas can be described as the product of the volume and the fraction. The dead space can be calculated according to Bohr's Formula.
                                          V            D                                V            E                          =                                            F                              A                                  CO                  ⁢                                                                          ⁢                  2                                                      -                          F                              E                                  CO                  ⁢                                                                          ⁢                  2                                                                          F                          A                              CO                ⁢                                                                  ⁢                2                                                                        (        2        )            
The dead space can be determined by means of this formula. A change in the size of the dead space can indicate pathological changes. In addition to the dead space, other volumes can be indicators of pathological changes in the respiratory system. As in the definition of the dead space, medical science divides the other volumes into different categories.
For the quantitative measurement of the different lung volumes, the following volume divisions have been selected. In this process, lung volumes for the measurement of which the elapsed time is decisive are defined as “dynamic” volumes. Volumes that are independent of the strength of the respiratory flow (i.e., respiratory flow per unit of time) are designated as “static.” Volumes that are composed of two or more volumes are designated “capacity.” FIG. 2 shows the different volumes and the related abbreviations indicated therein and hereinafter explained in greater detail. Breath volume, or tidal volume (Vt), is the inspiration or expiration volume, which in adults at rest is approximately 500 ml. Inspiration Reserve Volume (IRV) is the volume that can be additionally inhaled after normal inspiration. Expiration Reserve Volume (ERV) is the volume that can additionally be exhaled after a normal expiration. Residual Volume (RV) is the volume that remains in the lung after maximal expiration. Vital Capacity (VC) is the maximum volume that can be exhaled after normal expiration. Inspiration Capacity (IC) is the maximum volume that can be inhaled after normal expiration. Functional Residual Capacity (FRC) is the volume that is still contained in the lung after normal expiration. Total Capacity (TLC) is the maximum possible lung volume.
The FRC is important for an understanding of the equalization of the inspiration and expiration O2 and CO2 fraction, and for the objective of the present invention. If the fresh air were to flow directly into the alveoli without mixing with the residual volume contained in the lung, the respiratory gas fraction there would increase or decrease after every respiration phase. As a result of the greater residual volume, which is up to three times greater than the tidal volume, and the mixing effect that thereby occurs, only slight temporal fluctuations of the breathable gas fraction occur in the alveoli. Thus, the composition of the exhaled breathable air remains relatively constant. Together with the respiration frequency, the breath volume provides an additional important definition of respiratory physiology.
The respiratory minute volume (MV) is the product of the tidal volume or flow volume and the respiration frequency, and in a healthy adult at rest is approximately 7 liters per minute and increases under stress. The respiratory minute volume is an active component in determining how sharply PAO2 and PACO2 increase and decrease, although in isolation it is not an indicator of the effectiveness of the ventilation. If the composition of the dead space is taken into consideration, and assuming a rapid and very flat respiration with a tidal volume of 0.2 liters and a respiration frequency of 35 breaths per minute, there would be little or no ventilation of the alveolar space with fresh air. The alveolar ventilation (portion of the respiratory time volume that benefits the alveoli) is accordingly the defining variable.
The magnitude of the various volumes such as tidal volume and/or the respiratory minute volume is influenced by the respiratory mechanics. The term “respiratory mechanics” refers to the pressure-volume, the pressure-flow and the pressure-time and flow-time relationship. The four most important parameters of respiratory mechanics are compliance, resistance, respiration work and the I:E ratio. These parameters are important both on account of their changes in response to pathological conditions and on account of their usefulness as initiating points for accomplishing the objectives of the present invention.
The I:E ratio provides information on the ratio of the inspiration time and expiration time. FIG. 3 depicts a schematic illustration of the I:E ratio during respiration. Physiological values for the I:E ratio are between 1:1.5 and 1:2.5. In respiratory care, attempts are made to counteract pathological changes by effecting controlled changes in the positioning of the I:E ratio on the respirator. The ratio is influenced by, among other things, compliance and resistance.
Compliance is a measurement of the elastic properties of the respiratory apparatus. As a result of its elastic parenchymal cells and the surface tension of the alveoli, the lung is subject to tensile stress and is always attempting to reduce its volume. Work must be performed to overcome this tensile stress during inspiration. During expiration, the retraction of the lungs occurs largely passively. The following equations apply:
Compliance of Thorax and Lungs:
                              C                      TH            +            L                          =                  V                      P            Pul                                              (        3        )            Compliance of the ThoraxCompliance of the Lung:
                              C          TH                =                  V                      P            Pleu                                              (        4        )                                          C          L                =                              ∂            V                                ∂                          (                                                P                  Pul                                -                                  P                  Pleu                                            )                                                          (        5        )            The relationship among the three equations is:
                              1                      C                          TH              +              L                                      =                              1                          C              L                                +                      1                          C              TH                                                          (        6        )            
The measurement presents problems in actual practice, because the respiratory musculature has to be disregarded for this purpose. Generally, only the lung compliance CL is determined, so that after the inspiration, a defined volume of the larynx is opened, and simultaneously the pressure in the alveoli equals the atmospheric pressure. Equation (6) can then be simplified to:
                              C          L                =                              Δ            ⁢                                                  ⁢            V                                Δ            ⁢                                                  ⁢                          P              Pleu                                                          (        7        )            
The resistance of the non-elastic respiratory tract is composed of fractions including (1) flow resistances in the respiratory system; (2) non-elastic tissue resistance; and (3) inertia. In this case, the flow resistance of the respiratory system accounts for 90% of the total resistance, which means that the other two factors can be ignored for our purposes. The driving force for the flow is the pressure difference between the atmosphere and the alveoli. Both turbulent and laminar flows are present in the respiratory system. For the laminar flow, the Hagen-Poiseuille Law applies and, although it does not apply for turbulent flow, this law can be used for the total flow resistance.
                              V          .                =                              Δ            ⁢                                                  ⁢            P                    R                                    (        8        )            In the equation presented above, “R” is the respiratory system resistance and is a function of the viscosity of the gas, the length of the respiratory system and the cross section of the respiratory system. The cross section of the respiratory system is thereby decisive in obstructive diseases of the respiratory system and is proportional to the fourth power of the radius of the respiratory tract. Consequently the resistance of the respiratory tract increases by a factor of sixteen when the radius of the respiratory tract is reduced by one-half. Resistance and compliance together are deciding factors in the respiratory work that a person must perform during respiration.
Physical work is defined during respiration by the product “Pressure×Volume,” and is the work that must be performed to overcome the elastic and viscous resistance. In general, the following relationship applies:W=∫PdV  (9)FIG. 4 shows a pressure-volume curve during normal respiration at rest. The tidal volume is plotted on the ordinate, and the pressure difference between the atmosphere and the pleural cavity is plotted on the abscissa. At point “A,” there are no muscle forces that are producing pressure. The curve “AXB” corresponds to the inspiration. The work that is expended during inspiration is composed of “elastic work” and “friction work.” The expiration occurs passively, and the respiratory work required to overcome the flow resistances is taken over by the lung tissues (area “ABC”) that were previously extended. The respiratory mechanism is what provides for the actual function of respiration, the pulmonary gas exchange that makes it possible to supply the body with oxygen and the elimination of the decomposition products.
The pulmonary gas exchange describes O2 absorption and CO2 released by the blood from and to the alveolar air. The O2 absorption results from the quantity of O2 added, minus the quantity exhaled. The CO2 released from the blood equals the quantity of CO2 removed from the alveoli, i.e., exhaled. The gas exchange occurs by diffusion between the alveoli and the lung capillary blood. This process is described by Fick's First Law:
                    j        =                  D          ⁢                                    ∂              c                                      ∂              x                                                          (        10        )            Equation (10) indicates the magnitude of the particle flow (O2 and CO2 molecules). The particle flow is a function of the surface area and type of the diffusion medium (lung tissue) and of the temperature and concentration difference (difference between lung capillary blood and alveoli). The difference in concentration is directly proportional to the pressure difference of the respiratory gas fractions and the particle flow is therefore a function of the respiratory air that is supplied. The CO2 diffusion coefficient is approximately 23 times higher than that of oxygen, so that sufficient CO2 can be removed in spite of small CO2 partial pressure differences.
The oxygen absorbed by the blood is transported to the cells where it is converted into energy with the help of enzymes (consumption of O2). This process is called “metabolism.” The metabolic product which is generated is carbon dioxide and is in turn given up via the blood circulation to the lungs. The ratio between the CO2 released and O2 consumed is termed the Respiratory Quotient (RQ). In healthy individuals, the RQ is between 0.8 and 0.9. Normal values for CO2 release are in a range of approximately 300 ml per minute; the corresponding O2 consumption is approximately 250 ml per minute. An increasing CO2 production always results in an increasing O2 consumption, which can be triggered by physical exertion, among other things. The body needs more energy and therefore produces more CO2. The process of oxygen consumption and CO2 release is automated in all mammals and is subject to respiratory regulation.
Respiration is for the most part regulated by arterial chemo receptors. Sensors of this type are located in the glomus caroticum, in the aortic arches and in the brain stem itself. The PaCO2, PaO2 and the pH are recorded. When the PaCO2 or pH increases, or if the PaO2 value decreases, the respiratory minute volume increases. On the other hand, an increase in the O2 partial pressure leads only to a slight drop in ventilation. FIG. 5 shows the respiratory responses for different partial pressures of oxygen and carbon dioxide. In this case, the arterial CO2 partial pressure is probably the most effective driver of respiration. High CO2 partial pressures in humans are connected with a feeling of shortness of breath, until a narcotic effect occurs at values higher than 70 mmHg. As a result of the increased respiratory minute volume, the carbon dioxide diffused from the blood into the alveoli is exhaled, which leads to a drop in the arterial CO2 partial pressure. The partial pressure is therefore a function of the respiratory minute volume; on the other hand, the respiratory minute volume is a function of the partial pressure. Dependencies of this type are termed a closed-loop control system in both biology and in engineering. A closed-loop control system is a system that works automatically to control conditions and processes. In respiration it works, among other things, to keep the arterial CO2 partial pressure constant.
The central and reflective factors on respiration that contribute to respiratory regulation merit a more complete explanation here. As a result of these factors, gas transport and gas exchange are guaranteed only when the respiratory movements and cardiovascular functions work in harmony with one another. The cardiac output volume must be increased under stress, and actions such as coughing or sneezing require precise coordination with respiration. The central and reflective factors are not discussed in any further detail. Rather, the complex mechanism of respiration is simplified to make a simulation thereof possible.
Capnometry is the measurement of carbon dioxide. Capnography is the graphic representation of the CO2 measurement. In medicine, these measurement methods are used to measure the CO2 concentration of the expiration air and to indicate the CO2 concentration by recalculations in the form of partial pressure. The graphically illustrated curve, the capnogram, gives the medical technician information on CO2 production, pulmonary perfusion, alveolar ventilation and carbon dioxide elimination. The capnogram includes four segments. FIG. 6 shows a schematic capnogram and its constituent parts. Numeral 1 indicates the beginning of expiration, in which a CO2 concentration of zero is measured, which corresponds to the proportion of the gas that does not participate in the gas exchange. Numeral 2 indicates an area in which an increasing concentration is measured, which results from the mixed air from the anatomical dead space and the alveoli that participate in the gas exchange. Numeral 3 indicates an area known as the EtCO2 concentration. Numeral 4 indicates the inspiration phase, in which fresh air is detected which has a CO2 carbon dioxide concentration of practically zero.
The EtCO2 partial pressure in a healthy subject is between 25-40 mmHg, with an average of 36 mmHg. With a CO2 production of 300 ml and a respiration frequency of f=12 breaths per minute, the calculated CO2 release in the expiration air is 25 ml CO2 per respiration cycle. According to Formula (I) and an assumed tidal volume of 500 ml, the calculated EtCO2 value is 38 mmHg. The arterial CO2 partial pressure is 3-7 mmHg above the end-tidal partial pressure.
Desirably, the physiological basis of respiration should be similarly implemented in detail such that the respiratory response to a CO2 partial pressure can be accurately simulated. Areas of application of lung simulators are the testing of respiratory equipment and the training of medical personnel. These simulators are also used in research and development as lung models for the validation of new equipment and therapeutic procedures. Basically, there are two types of lung simulators-simulation of lung mechanics by means of bellows and simulation of lung mechanics by means of a piston and cylinder.
Innovative therapeutic procedures, respiration modes and other innovations always create new requirements for the technology of lung simulators. Simply simulating respiratory mechanics is no longer sufficient. Lung simulators that perform the tasks of the lung such as gas exchange or respiratory regulation are required. For the technological implementation of these requirements, methods must be defined and implemented that can realize the metabolism of oxygen and carbon dioxide. Three exemplary methods are fuel cell technology, molecular sieve and combustion. Prior research and tests on these three methods have shown that their implementation in a lung simulator is too dangerous, complicated or expensive. The state of the art is to simulate the respiratory gas by mixing gases. The air drawn into the lung simulator during the inspiration is “ejected” and replaced by a mixture of gases consisting of CO2, N2 and O2. Market research has shown that, for the majority of potential customers of lung simulators, the simulation of the respiratory response to a physiological CO2 partial pressure may be sufficient.
For the simulation of the respiratory response, it is first necessary to describe the relatively complicated process of respiratory regulation on the basis of a simplified model. FIG. 7 depicts a simplified block diagram of a closed-loop control system to illustrate the processes associated with respiration.
The metabolism represents cell respiration, the part in which, by way of the consumed oxygen, energy is provided for the body and carbon dioxide is formed as a decomposition product. CO2 diffuses from the oxygen-poor blood into the alveolar air. The arrow that exits the lung-heart system represents the respiratory gases (expiration/inspiration). After the blood has been saturated with oxygen and the CO2 has been eliminated, the blood continues to flow through the body and to supply it with O2. The arterial, oxygen-rich blood flows through the chemo-receptors which register the pH as well as the arterial oxygen and CO2 partial pressure. If this value deviates from the specified value, receptors emit a signal which increases or decreases the tidal volume and respiration frequency. The changed respiratory minute volume also changes the rate of elimination of carbon dioxide and the consumption rate of oxygen, so that the measured partial pressures once again correspond to the specified range of values. The respiratory minute volume is composed of the respiration frequency and tidal volume. The respiration frequency and tidal volume have a variance which is a function of sex, age, state of health, size, weight and fitness. Independent of the factors listed above, however, the respiration frequency and tidal volume are in a linear relationship with the CO2 content. However, the increases of respiration frequency and tidal volume are different and are a function of the factors cited above.
FIG. 8 shows one example of the response of the parameters of tidal volume (C), frequency (B), respiratory minute volume (A) and EtCO2 partial pressure (D). The illustrated extract originates from six young, healthy men, although it is not representative. The analysis of graphs “B” and “C” shows a linear increase with increasing CO2. The EtCO2 partial pressure experiences only a slight increase with increasing CO2 flow. If the respiratory minute volume did not increase in spite of increased CO2 production, that would lead to a super-saturation (acidosis) of the blood and therefore to serious complications. If the stress does not continue to increase, the CO2 production does not continue to increase either, which means that an equilibrium is established between the CO2 partial pressure and the respiratory minute volume.
FIG. 9 shows that under constant stress, the respiratory minute volume increases and reaches a plateau when there is equilibrium between respiratory minute volume (MV) and CO2 partial pressure. When the test subject is then no longer subjected to stress, the respiratory minute volume decreases rapidly relative to the increase until normal values are reached.
In summary, the human respiratory system responds, among other parameters, to changes in the metabolic rate by appropriately altering both breath rate (bpm) and tidal volume (Vt) of each breath. It has been determined that CO2 partial pressures in the blood are, aside from O2 levels, the most significant parameters in a control system. The target for the combination of bpm and Vt attained is determined by the minimum amount of respiratory work to be performed, following a principle of energy conservation often found in natural processes. For the purpose of simulating a self-regulating respiratory system, the response of a patient to CO2 has been modeled and implemented in the past using a conventional bellows-based lung model modified to generate patient breathing effort. The resulting human patient simulators (HPS) have used gas substitution as their method of generating true-to-life exhaled gas compositions. The delivery of CO2 simulating a patient's exhaled CO2 for the purpose of generating an approximately true-to-life reading in capnography equipment connected to respiratory simulators has been described and used for a considerable amount of time. To improve the distribution of CO2 injected into a lung simulator bellow, small fans have been used. The waveform of CO2 and readings for the monitoring parameter EtCO2 are compromised when a lung model with a small FRC or dead space compared to an actual patient is used. Gas substitution is a complex method for generating exhaled gas compositions in a human patient simulator and exceeds the required fidelity in many cases.
As previously discussed, lung simulators play an important role in product qualification of respiratory devices. Additionally, lung simulators may be used to teach ventilator management to respiratory therapists. Therefore, it is desirable to make advances in the field of lung simulators by improving the lung simulation to be more realistic by accounting for a patient's response to a physiological CO2 partial pressure, for example.